Aim. Chlorogenic acid (CGA) is a natural polyphenolic compound found in human dietary products. Previous studies have confirmed that CGA has many biological activities, such as regulating glucose and lipid metabolism and improving insulin resistance. However, its underlying mechanisms of action remains unclear. Here, we demonstrate the protective effects and molecular mechanisms of action of CGA in reducing weight gain and hyperlipidemia in mice fed with a high‐fat diet (HFD). Methods and Results. C57BL/6 mice were fed with normal chow or HFD; half of the mice in each group received CGA treatment by oral gavage for 16 weeks. CGA treatment was found to significantly inhibit HFD‐induced weight gain and hyperlipidemia and increased energy expenditure by promoting the expression of genes involved in thermogenesis and mitochondrial biogenesis. Furthermore, CGA was shown to inhibit the enterohepatic farnesoid X receptor (FXR) fibroblast growth factor 15 (FGF15) pathway and changes serum bile acid (BA) pool, thereby contributing to the increased expression of cholesterol 7 α‐hydroxylase (CYP7A1). Conclusions. CGA increases the metabolic elimination of cholesterol by inhibiting the enterohepatic FXR/FGF15 pathway.

INTRODUCTION: Systemic inflammation and lipid metabolism disturbances are important hallmarks of the onset and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to explore the association of lymphocyte-high-density lipoprotein-cholesterol ratio (LHR), monocyte-HDL-C ratio (MHR), neutrophil-HDL-C ratio (NHR), and platelet-HDL-C ratio (PHR) with MASLD and significant liver fibrosis using NHANES 2017–2020 data. METHODS: LHR, MHR, NHR, and PHR were calculated based on complete blood count parameters and serum HDL-C. MASLD and liver fibrosis were diagnosed based on transient elastography. Multivariate logistic regression analyses were used to explore these associations, and receiver operating characteristic was used to compare the predictive power of these markers. RESULTS: A total of 8,341 participants were included, and the prevalence of MASLD and significant liver fibrosis was 45.1% and 11.57%, respectively. In fully adjusted models, log-transformed LHR, MHR, NHR, and PHR were positively associated with the odds of MASLD (odds ratio 1.853, 1.685, 1.470, and 1.879, respectively) and significant liver fibrosis (odds ratio 1.570, 1.425, 1.396, and 1.384, respectively) (all P < 0.05). Most of these associations were nonlinear, and significant positive correlations existed only after their respective inflection points. The association of LHR with significant liver fibrosis was more pronounced in men. Receiver operating characteristic analysis showed that LHR/NHR was superior in predicting MASLD, whereas MHR/NHR distinguished significant liver fibrosis better than other markers. DISCUSSION: LHR, MHR, NHR, and PHR were independently associated with MASLD and liver fibrosis in US adults and may serve as emerging predictors. Future cohort studies are needed to confirm these findings and explore clinical predictive value.

The disturbance of gut microbiota is closely related to the occurrence and development of inflammatory bowel disease (IBD), which can be improved by the supplementation of prebiotics. The therapeutic benefits of exclusive enteral nutrition (EEN) on patients with IBD are variable, and it has adverse effects on gut microbiota. Therefore, it is necessary to explore the efficacy of EEN combined with prebiotics on colitis and gut microbiota. In our study, mice were administered distilled water containing 4% dextran sodium sulfate (DSS) to induce colitis, then fed with normal water, EEN, EEN combined with isomaltooligosaccharide (IMO), EEN combined with fructo-oligosaccharide (FOS), and EEN combined with polydextrose (POL) for 1 week, respectively. The results revealed that EEN combined with prebiotic treatments showed more benefits in alleviating DSS-induced colitis than EEN treatment, among which FOS exhibited superior efficacy, including reducing disease activity index (DAI) (8.67 ± 0.52 vs 9.67 ± 0.82) and preventing colon shortening (7.23 ± 0.33 vs 6.43 ± 0.28 cm). Compared with the DSS group (7.00 [interquartile range, IQR: 5.75–8.25]), the histological score of IMO (2.50 [IQR: 2.00–4.00]), FOS (2.50 [IQR: 0.00–3.00]), and POL (2.00 [IQR: 1.50–7.25]) groups was obviously lower. In addition, prebiotics as adjunctive treatment increased more beneficial species than EEN treatment. Compared with the DSS group, POL adjuvant treatment enhanced the Simpson index, altered the overall structure of the gut microbiota, and IMO adjuvant treatment improved the F/B ratio (0.28 [IQR: 0.12–0.64] vs 1.06 [IQR: 0.87–2.82]). This study proved that prebiotics as adjuvant therapy improved colitis by regulating gut microbiota, providing a foundation for clinical application. IMPORTANCE: We demonstrated the superior efficacy of prebiotics as adjuvant therapy in improving clinical outcomes (body weight, colonic length, disease activity index, and histological score) and modulating the structure and composition of gut microbiota in dextran sodium sulfate-induced colitis in mice.